Respiratory omics for early detection of COPD-to-lung cancer transition: mechanisms, biomarkers and clinical translation.

Chronic obstructive pulmonary disease (COPD) substantially increases the risk of lung cancer, yet biomarkers capable of identifying malignant transition before radiological abnormalities become evident remain lacking. Respiratory omics has emerged as a promising non-invasive approach for monitoring dynamic molecular alterations during disease progression through the analysis of exhaled volatile organic compounds (VOCs) and exhaled breath condensate (EBC). This review summarizes current evidence on respiratory biomarkers associated with COPD-to-lung cancer transition, emphasizing the biological mechanisms underlying their dynamic evolution and their potential applications in early detection and risk stratification. Rather than considering COPD and lung cancer as separate diseases, we discuss respiratory biomarker changes across the disease continuum and highlight their translational value for identifying high-risk individuals. Finally, we outline the major challenges limiting clinical implementation, including biomarker standardization and prospective validation, and discuss future directions involving multi-omics integration, artificial intelligence, and precision surveillance. Respiratory omics has the potential to advance non-invasive risk assessment and facilitate earlier intervention for COPD-associated lung cancer.